Ruxolitinib in the treatment of polycythemia vera: patient selection and special considerations.

The discovery of JAK2 V617F mutation in the mid-2000s started to fill the gap between clinical presentation of polycythemia vera (PV), first described by Vaquez at the end of the 19th century, and spontaneous erythroid colony formation, reported by Prchal and Axelrad in the mid-1970s. The knowledge on this mutation brought an important insight to our understanding of PV pathogenesis and led to a revision of the World Health Organization diagnostic criteria in 2008. JAK-STAT is a major signaling pathway implicated in survival and proliferation of hematopoietic precursors. High prevalence of JAK2 V617F mutation among myeloproliferative neoplasms (>95% in PV and ~50% in primary myelofibrosis and essential thrombocythemia) together with its role in constitutively activating JAK-STAT made JAK2 a privileged therapeutic target. Ruxolitinib, a JAK 1 and 2 inhibitor, has already proven to be efficient in relieving symptoms in primary myelofibrosis and PV. In the latter, it also appears to improve microvascular involvement. However, evidence regarding its potential role in altering the natural course of PV and its use as an adjunct to current standard therapies is sparse. Therapeutic advances are needed in PV as phlebotomy, low-dose aspirin, cytoreductive agents, and interferon alpha are the only therapeutic tools available at the moment to influence outcome. Even though several questions are still unanswered, this review aims to serve as an overview article of the potential role of ruxolitinib in PV according to current literature and expert opinion. It should help hematologists to visualize the place of this tyrosine kinase inhibitor in the field of current practice and offer criteria for a careful patient selection

Direct Oral Anticoagulant Drugs: On the Treatment of Cancer-Related Venous Thromboembolism and their Potential Anti-Neoplastic Effect.

Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism

Aloe vera extract as a promising treatment for the quality maintenance of minimally-processed table grapes

The effect of an edible film obtained from a commercial Aloe vera extract, on the quality maintenance of minimally processed grapes belonging to three different cultivars (Sugar One, Victoria and Black Magic) was evaluated by enzymatic (PPO, PME, β-GAL), physicochemical (pH, acidity, °Brix), and sensorial methods. All the analyzed parameters were measured in extracts obtained from minimally processed grapes packaged in ordinary atmosphere and stored at 4 °C for 15 days. Samples dipped into Aloe vera showed significant differences (p≤0.05) compared to untreated ones. The determination of such parameters and the evaluation of consumer acceptability were helpful to determine the effectiveness of the post-harvest treatment with Aloe vera for a storage period of 15 days. © 2015, Sociedade Brasileira de Ciencia e Tecnologia de Alimentos, SBCTA. All rights reserved

Autoimmune Hemolytic Anemia and Pulmonary Embolism: An Association to Consider.

Autoimmune hemolytic anemia (AIHA) is increasingly recognized as a strong risk factor for venous thrombosis. However, there are currently no guidelines on thromboembolism prevention and management during AIHA. Here, we describe the case of a patient with AIHA and pulmonary embolism and resume the current knowledge on epidemiology, risk factors, treatment, and pathophysiology of thrombosis during AIHA, as well as new therapeutic perspectives to prevent thrombus formation during AIHA

Identification of High Platelet Reactivity Despite ADP P2Y12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve.

Introduction Response to ADP P2Y <sub>12</sub> receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y <sub>12</sub> assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y <sub>12</sub> platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y <sub>12</sub> assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y <sub>12</sub> assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y <sub>12</sub> assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y <sub>12</sub> and PFA-P2Y is necessary for optimal detection of HPR

Transverse momentum fluctuations and percolation of strings

The behaviour of the transverse momentum fluctuations with the centrality of the collision shown by the Relativistic Heavy Ion Collider data is naturally explained by the clustering of color sources. In this framework, elementary color sources --strings-- overlap forming clusters, so the number of effective sources is modified. These clusters decay into particles with mean transverse momentum that depends on the number of elementary sources that conform each cluster, and the area occupied by the cluster. The transverse momentum fluctuations in this approach correspond to the fluctuations of the transverse momentum of these clusters, and they behave essentially as the number of effective sources.Comment: 16 pages, RevTex, 4 postscript figures. Enhanced version. New figure

Rapid malignant progression of an intraparenchymal choroid plexus papillomas

Background: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. Case Description: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. Conclusion: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach